Broccoli extract improves chemotherapeutic drug efficacy against head–neck squamous cell carcinomas
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The efficacy of cisplatin (CIS) and 5-fluorouracil (5-FU) against squamous cell carcinomas of the head and neck (SCCHN) remains restricted due to their severe toxic side effects on non-cancer (normal) tissues. Recently, the broccoli extract sulforaphane (SF) was successfully tested as a combination therapy to target cancer cells. However, the effect of lower doses of CIS or 5-FU combined with SF on SCCHN remained unknown. This study tested the chemotherapeutic efficacies of SF combined with much lower doses of CIS or 5-FU against SCCHN cells aiming to reduce cytotoxicity to normal cells. Titrations of SF standalone or in combination with CIS and 5-FU were tested on SCCHN human cell lines (SCC12 and SCC38) and non-cancerous human cells (fibroblasts, gingival, and salivary cells). Concentrations of SF tested were comparable to those found in the plasma following ingestion of fresh broccoli sprouts. The treatment effects on cell viability, proliferation, DNA damage, apoptosis, and gene expression were measured. SF reduced SCCHN cell viability in a time- and dose-dependent manner. SF-combined treatment increased the cytotoxic activity of CIS by twofolds and of 5-FU by tenfolds against SCCHN, with no effect on non-cancerous cells. SF-combined treatment inhibited SCCHN cell clonogenicity and post-treatment DNA repair. SF increased SCCHN apoptosis and this mechanism was due to a down-regulation of BCL2 and up-regulation of BAX, leading to an up-regulation of Caspase3. In conclusion, combining SF with low doses of CIS or 5-FU increased cytotoxicity against SCCHN cells, while having minimal effects on normal cells.
KeywordsHead and Neck cancer Carcinoma, squamous cell Sulforaphane Drug therapy Apoptosis DNA damage
We would like to thank Murali Ramamoorthi, Andre Charbonneau, Mohamed Nur Abdallah, and Gulshan Sunavala-Dossabhoy for donating human SCC, fibroblasts, HGEPC, and NS-SV-AC, respectively. We also thank Younan Liu and Mohammed Bakkar for helpful discussion in setting up preliminary experiments.
This work was partly funded by Canadian Institutes of Health Research (CIHR Grant 119585), Natural Sciences and Engineering Research Council of Canada (NSERC Grant 05247), MJW Kim research fund, and the Ministry of Higher Education in Egypt (MOHE postgraduate studies funding).
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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